Antibiotics without selectivity may destroy the friendly microbes in the human microbiome that helps fight pathogens and maintain homeostasis of microbiome. The fermentation product (yogurt) of friendly bacteria in human intestine promotes a healthy digestive system. However it is not fully clear whether friendly microbes in human skin have the fermentation activity and whether ferments including short-chain fatty acids (SCFAs) of these microbes have probiotic activities to maintain the homeostasis of the skin microbiome. We envision that, during the development of acne vulgaris, skin microorganisms such as Staphylococcus epidermidis (S. epidermidis) irregularly migrate from the outer surface of the skin into the enlarged/inflamed follicle, where opportunistic strains of Propionibacterium acnes (P. acnes) exclusively habitate. After follicle wall ruptures, bacteria enter the dermis and develo acne lesions with an anaerobic microenvironment which triggers skin microorganisms to undergo fermentation using carbohydrates as carbon sources naturally produced in skin. Results in our recent publication have illustrated that S. epidermidis in human fingerprints can ferment glycerol and create inhibition zones to repel a colony of overgrown P. acnes, a Gram-positive bacterium highly associated with acne vulgaris. The succinic acid in the fermented media of S. epidermidis efficiently hinders the growth of P. acnes in vitro and in mice. We have recently collected acne biopsies in collaboration with Dr. Tissa R. Hata, a Director of the Dermatology Clinical Trials Unit at University of California, San Diego (UCSD). In Specific Aim 1, we will select the microorganisms with fermentation activities within acne lesions as acne probiotics, and examine the efficacy of acne probiotics in suppressing the growth of various clinical P. acnes strains. In Specific Aim 2, we will identify the SCFAs in the fermentation products of probiotic microorganisms via nuclear magnetic resonance (NMR) analysis, and use ex vivo human acne explants to validate the anti-P. acnes activities of acne probiotics. In Specific Aim 3, we will test whether acne probiotics cause unintended consequences of perturbing the growth of other skin commensals, and investigate the responses of skin cells to acne probiotics. The use of acne probiotics as innate anti-P. acnes therapeutics is in compliance with evolutionary medicine and has a lower risk of induction of resistant P. acnes and other side-effects because P. acnes/skin commensal interference may occur naturally within lesions of acne vulgaris.